Hormone conditioned cancer chemotherapy for recurrent breast cancer prolongs survival

Left suprarenal-inferior mesenteric venous shunt (Inokuchi) was prescribed for 80 patients with recurrent breast cancer and the efficacy of hormone coditioned cancer chemotherapy was assessed. The patients were separated into 3 groups according to the historical regimen of combined chemotherapy: Group I; surgical hormone therapy alone, Group II; surgery plus short term chemotherapy, and Group III; surgery plus long term chemotherapy. The 5 year survival rate of the responsive patients to the surgical hormone therapy was as high as 84.6 per cent in Group III, as compared to that of Groups I and II, 41.7 per cent and 16.7, respectively. Survival was not prolonged in non-responsive patients, regardless of the group. These findings indicate that surgical hormone therapy combined with postoperative long term cancer chemotherapy is a valid and effective method for treating recurrence of breast cancer.     

Oncoplastic Surgery: Pushing the Limits of Breast‐Conserving Surgery

In recent decades, the surgical management of breast cancer has steadily and considerably improved. Mutilating procedures have given way to more individualized surgical approaches aiming to preserve the breast as much as possible. For large tumors, preoperative chemotherapy is a major tool, but emerging oncoplastic surgery techniques are also a new approach in the armamentarium of breast cancer surgery, as a third option between conventional breast‐conserving surgery and mastectomy. As this new treatment modality allows wider margin excision, it reduces the need for re‐excision procedures and possibly increases breast conservation rates by extending the indications of breast‐conserving surgery. This review will provide an overview of current practices and clinical data available to date on oncoplastic surgery.     

Hormone conditioned cancer chemotherapy for recurrent breast cancer prolongs survival

Left suprarenal-inferior mesenteric venous shunt (Inokuchi) was prescribed for 80 patients with recurrent breast cancer and the efficacy of hormone conditioned cancer chemotherapy was assessed. The patients were separated into 3 groups according to the historical regimen of combined chemotherapy: Group I; surgical hormone therapy alone, Group II; surgery plus short term chemotherapy, and Group III; surgery plus long term chemotherapy. The 5 year survival rate of the responsive patients to the surgical hormone therapy was as high as 84.6 per cent in Group III, as compared to that of Groups I and II, 41.7 per cent and 16.7, respectively. Survival was not prolonged in non-responsive patients, regardless of the group. These findings indicate that surgical hormone therapy combined with postoperative long term cancer chemotherapy is a valid and effective method for treating recurrence of breast cancer.     

Clinicopathologic features of hormone‐receptor‐positive breast cancer patients with late recurrence

The number of long‐term breast cancer survivors with a risk of late recurrence is increasing. Hormone‐receptor‐positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone‐receptor‐positive patients have greater risks of late recurrence. Hormone‐receptor‐positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow‐up of 10.9 years (range, 5.1‐23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P < .001), whereas 1‐3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P < .001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease‐free survival than tamoxifen (10‐year disease‐free survival: 97.6% vs 89.7%, P = .0955). High nodal involvement was significantly correlated with late recurrence in hormone‐receptor‐positive breast cancer patients. Hormone‐receptor‐positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.     

Demonstration of erectile management techniques to men scheduled for radical prostatectomy reduces long-term regret: a comparative cohort study

Study Type – Outcomes (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Patients with localized prostate cancer face a bewildering number of treatment choices. Modern technology and innovation in treatment techniques have seen patient expectations rise exponentially, leading to an increase in regret of treatment choice. This study has shown that the demonstration of erectile function techniques helps inform decision‐making and reduce long‐term regret of treatment choice in localized prostate cancer.

OBJECTIVE

? To determine whether preoperative demonstrations of intracavernosal and vacuum therapies for erectile dysfunction (ED) influence the decision of treatment choice, reducing long‐term regret.

PATIENTS AND METHODS

? In all, 82 consecutive men with localized prostate cancer, scheduled for radical prostatectomy and reporting an International Index of Erectile Function score of >21, were prospectively enrolled at a single cancer centre. ? Following standard preoperative counselling, half of the men were invited to attend a further consultation for intracavernosal and vacuum therapy demonstrations. ? All patients were evaluated pretreatment and then 3 monthly using the five‐point International Index of Erectile Function score and the 14‐item Hospital Anxiety and Depression scale. ? At 12 months treatment choice changes were recorded and patients were assessed for treatment choice regret using Clark’s validated two‐item regret questionnaire. Statistical analysis was performed using the Mann–Whitney and Fisher’s exact tests. Results were compared with a control population of 41 men who did not undergo additional ED counselling.

RESULTS

? In all, 8/41 men (19%) changed their treatment choice, opting for brachytherapy rather than radical prostatectomy. ? Only 1/41 in the control population changed their decision before surgery. ? At 1 year, one patient (2%) in the intervention group expressed regret at his treatment choice (radical prostatectomy) compared with eight (20%) in the control group (P= 0.03, two‐sided Fisher’s exact test); ED was identified as the major cause of this regret.

CONCLUSION

? Preoperative demonstrations of ED therapies can optimize decision making in prostate cancer and help reduce long‐term regret.     

Outcomes of breast cancer in patients who use alternative therapies as primary treatment

BACKGROUND: Some breast cancer patients opt for alternative treatments in place of conventional treatments. The lack of published data on the outcome of this strategy may contribute to this trend. METHODS: A chart review was performed of breast cancer patients who refused or delayed standard surgery, chemotherapy, and/or radiation therapy. Prognosis was calculated for recommended and actual therapy. RESULTS: Thirty-three patients were included in the analysis. Of 11 patients who initially refused surgery, 10 developed disease progression. Of 3 patients who refused adequate nodal sampling, 1 developed nodal recurrence. Of 10 patients who refused local control procedures, 2 developed local recurrences and 2 died of metastatic disease. By refusing chemotherapy, 9 patients increased their estimated 10-year mortality rate from 17% to 25%. CONCLUSIONS: Alternative therapies used as primary treatment for breast cancer are associated with increased recurrence and death. Homeopathy instead of surgery resulted in disease progression in most patients. These data may aid patients who are considering alternative therapies.     

Educational Review Hormone Replacement Therapy and Breast Cancer

The use of hormone replacement therapy by postmenopausal women with a history of breast cancer is a subject of considerable controversy. There are no scientific studies that have appropriately examined the issue, and current practice is often based on inferences from indirect evidence, anecdotal experience, and personal bias. Our understanding of the effects of exogenous, as well as endogenous, hormones on normal and neoplastic breast tissue provides some insights but is not an appropriate basis for clinical practice. The effects of exogenous hormone replacement on the overall health of postmenopausal women, including psychosocial issues, cardiovascular risks, and the morbidity of osteoporosis, must be understood before patients can be counseled appropriately. Treatment of patients must be individualized. The rapidly expanding area of nonhormonal therapies for the treatment of postmenopausal health risks and the treatment of symptomatic complaints in postmenopausal women has already led to a reevaluation of the use of exogenous hormones among all women. A prospective randomized trial that examines the effects of hormone replacement on women with a history of breast cancer is currently underway and will provide valuable data to address these issues. The aim of this review is to outline the scientific basis for the association between estrogen and breast cancer and to provide a framework in which individualized recommendations concerning the use of hormone replacement therapy can be made for patients with breast cancer.     

Machine learning with PROs in breast cancer surgery; caution: Collecting PROs at baseline is crucial

As high breast cancer survival rates are achieved nowadays, irrespective of type of surgery performed, prediction of long‐term physical, sexual, and psychosocial outcomes is very important in treatment decision‐making. Patient‐reported outcomes (PROs) can help facilitate this shared decision‐making. Given the significance of more personalized medicine and the growing trend on the application of machine learning techniques, we are striving to develop an algorithm using machine learning techniques to predict PROs in breast cancer patients treated with breast surgery. This short communication describes the bottlenecks in our attempt to predict PROs.     

Quantitative Progesterone Receptor Expression and Efficacy of Anti‐estrogen Therapy in Breast Cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti‐estrogen therapies is well‐established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti‐estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme‐linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan‐Meier actuarial survival analysis and the log‐rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti‐estrogen treated patients, when the ER and PR positivity cut‐off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR? tumors for both breast cancer‐free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti‐estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti‐estrogen therapy in breast cancer patients.     

Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer

The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease.The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy.However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research.This review focuses on current and emerging treatments for HR+ metastatic breast cancer.     

Use of the neo-adjuvant exemestane in post-menopausal estrogen receptor-positive breast cancer: A randomized phase II trial (PTEX46) to investigate the optimal duration of preoperative endocrine therapy

PurposeThe optimal treatment duration time and the causal relationship between neoadjuvant endocrine therapy and clinical response are not clear. Therefore, we conducted the present study to investigate the potential benefits of neoadjuvant exemestane therapy with the goal of identifying the optimal treatment duration.MethodsThis study was conducted at three hospitals, as a multicenter, randomized phase II trial(UMIN000005668) of pre-operative exemestane treatment in post-menopausal women with untreated primary breast cancer. Fifty-one post-menopausal women with ER-positive and/or PgR-positive invasive breast cancer were randomly assigned to exemestane for 4 months or 6 months. Clinical response, pathological response, and decisions regarding breast-conserving surgery were the main outcome measures.ResultsOf the 52 patients that enrolled, 51 patients underwent surgery. Of those, 26 and 25 patients had been treated with exemestane for 4 and 6 months, respectively. Treatments were performedat 3 hospitals in Japan between April 2008 and August 2010. The response rates as assessed by clinical examination were 42.3% and 48.0% for 4 and 6 months of treatment, respectively. Pathological responses (minimal response or better) were observed in 19.2% and 32.0% of patients, and breast-conserving surgery was performed on 50.0% and 48.0% of patients from the 4 and 6 month treatment groups, respectively.ConclusionThe results of this study demonstrate that responses were equal to 4 or 6 months of exemestane treatment. Therefore, we propose that the rates of breast-conserving surgery could be maximized by 4 months of treatment. Furthermore, in addition to using exemestane as a preoperative treatment in post-menopausal women with ER-positive breast cancer, we envision administering the drug over the long term under careful clinical supervision.     

Current status of primary pharmacotherapy and future perspectives toward upfront therapy for metastatic hormone‐sensitive prostate cancer

Since 1941, androgen deprivation therapy has been the primary treatment for metastatic hormone‐sensitive prostate cancer. Androgen deprivation therapy consists of several regimens that vary according to therapeutic modality, as well as treatment schedule. Androgen deprivation therapy initially shows excellent antitumor effects, such as relief of cancer‐related symptoms, tumor marker decline and tumor shrinking. However, most metastatic hormone‐sensitive prostate cancer cases eventually develop castration resistance and become lethal. Taxanes, such as docetaxel and cabazitaxel, as well as novel androgen receptor‐targeting agents, such as abiraterone acetate and enzalutamide, have emerged for metastatic castration‐resistant prostate cancer. The concept and principle of primary therapy for metastatic hormone‐sensitive prostate cancer has remained unchanged for decades. Recently, upfront docetaxel chemotherapy has been shown to prolong overall survival in men with metastatic hormone‐sensitive prostate cancer, and would lead to a paradigm shift in primary pharmacotherapy for metastatic hormone‐sensitive prostate cancer. This raises the possibility of upfront use of taxanes, as well as novel androgen receptor‐targeting agents combined with androgen deprivation therapy. The present review summarizes the current status of primary pharmacotherapy for metastatic hormone‐sensitive prostate cancer, and discusses future perspectives in this field.     

Outcome of small invasive breast cancer with no axillary lymph node involvement

Abstract: The prognosis and need or not for adjuvant therapy in patients with small breast tumors (≤1 cm N0) is the subject of controversy as regards the clinical benefit obtained, toxicity, and the economical costs generated. A retrospective analysis was made of 238 patients with early‐stage breast cancer (pT1 ≤ 1 cm N0M0) diagnosed between January 1993 and May 2008. As regards the systemic adjuvant treatments provided, (a) 122 (51%) received no treatment, (b) 102 (43%) received hormone therapy, (c) 9 (4%) chemotherapy, and (d) 5 (2%) received both hormone therapy and chemotherapy. An analysis was made of disease‐free survival (DFS) and breast cancer‐specific survival in our series of patients, and of their correlation to clinicopathological factors (age, tumor size, histological grade, estrogen receptor (ER) expression, HER‐2 overexpression, and systemic adjuvant therapy). The median follow‐up of this cohort was 63 months (range 5–145). Some type of relapse was recorded in 4.2% of the patients (six patients presented local recurrence in all cases subjected to rescue treatment with surgery and/or radiotherapy, three patients developed distant metastases, and one patient presented a resected local recurrence followed by systemic relapse). The 5 year DFS was 96%, and the 5 year breast cancer‐specific survival was 99.6%. A univariate analysis was made of the clinicopathological variables and their association to DFS. None of the variables was seen to be significantly correlated to shorter DSF except for an association between HER‐2 overexpression and poor outcome borderline significance (p = 0.07). The prognosis of our pT1 ≤ 1 cm N0M0 tumors was excellent, although the absence of systemic adjuvant therapy in one‐half of the patients.     

Neo-adjuvant hormonal therapy

Abstract:  Neo-adjuvant endocrine therapy has opened new alternatives for locally advanced breast cancer. Such therapy, which has permitted us to expand the treatment role of neo-adjuvant therapies, may be of great benefit to patient groups such as the elderly, those not suited for chemotherapy, and those whose response may not be optimal. This therapy also may be able to help us identify agents that could improve outcomes in the adjuvant setting as well as possible biologic predictors for outcome. The latest generation of endocrine therapy for breast cancer, aromatase inhibitors, has proved superior to tamoxifen in terms of toxicity and efficacy in the adjuvant setting and is currently being studied in other clinical trials. Current findings indicate that these agents are less toxic and better tolerated than neo-adjuvant chemotherapy and that third-generation anti-hormomal therapy offers improved tumor response compared with tamoxifen, which has resulted in increased breast conserving surgery. Biomarker findings of improved response in tumors that are both estrogen receptor positive and HER-2 positive as well as progesterone receptor positivity only will be important for planning future selective treatment and clinical trials.     

影像学对直肠癌新辅助治疗后分期的评估价值

局部进展期直肠癌的标准治疗方案是术前新辅助放化疗联合手术的综合治疗.高达30％的局部进展期直肠癌患者经过新辅助治疗后可以达到病理完全缓解（pCR）.研究显示,病理完全缓解的病例,局部复发率低、预后较好.故有学者提出,对新辅助治疗后达到部分或完全临床缓解（cCR）的病例,可分别采取手术局部切除术或严密随访的治疗方案,以避免根治性手术带来的风险或功能障碍.当前,影像学检查能对新辅助治疗前的直肠癌进行准确分期,但治疗所引起的肿瘤及周围组织的改变,会影响治疗后再分期的准确性,尤其是预测pCR的准确性一直比较低.如何在术前判定新辅助治疗后达到pCR,是目前人们关注的问题.本文以术后病理结果为标准,就当前常用影像学技术在直肠癌新辅助治疗后分期诊断中的价值及pCR的预测作一简要综述。     

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x‐rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long‐term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.     

Hypofractionated radiation treatment for breast cancer: The time is now

While there is now Level I data with long‐term follow‐up supporting the routine use of hypofractionated (HF) whole‐breast radiation therapy (WBRT) after breast‐conserving surgery, its adoption has been slow and variable. This article will review the literature supporting the efficacy and safety of hypofractionated radiation for breast cancer, discuss the radiobiological rationale specific to breast tumors, and make an argument for justifying the routine adoption of shorter, HF‐WBRT courses when delivering breast radiation. Data using HF with regional nodal irradiation and in the post‐mastectomy setting will also be reviewed. The aim is to provide an in‐depth understanding of the use of hypofractionated radiation therapy for breast cancer, its applicability, and topics warranting future research.     

原发性肝癌综合治疗的进展和热点

原发性肝癌(本文特指肝细胞癌,以下简称肝癌)的治疗原则是以手术为主的综合治疗。围绕提高根治性手术切除率和降低术后复发率等难题,肝癌的转化治疗、新辅助治疗和术后辅助治疗应运而生,极大地丰富了综合治疗的内涵,也成为研究热点。肝癌侵袭转移性强且常合并肝硬化等,综合治疗必不可少,但因手术适应证仍存在争议、个体间异质性大等原因,三种治疗方式尤其是转化治疗和新辅助治疗在概念和治疗方式上并非泾渭分明。治疗目标不同导致治疗方式选择、疗程长短和评估标准等也不同。结合临床实践,笔者分类论述肝癌的转化治疗、新辅助治疗和术后辅助治疗等最新进展和热点问题,期待开展更多研究获得临床循证医学证据规范综合治疗,从而成为提高肝癌诊断与治疗效果的突破口。     

Is intermittent androgen‐deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen‐deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side‐effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first‐line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high‐risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short‐ and long‐term side‐effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side‐effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT‐related side‐effects, and, to a degree, their impact on patient health‐related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long‐term complications associated with ADT.